Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Ultrasound vs. Computed Tomography for Severity of Hydronephrosis and Its Importance in Renal Colic

Introduction: Supporting an “ultrasound-first” approach to evaluating renal colic in the emergency department (ED) remains important for improving patient care and decreasing healthcare costs. Our primary objective was to compare emergency physician (EP) ultrasound to computed tomography (CT) detection of hydronephrosis severity in patients with suspected renal colic. We calculated test characteristics of hydronephrosis on EP-performed ultrasound for detecting ureteral stones or ureteral stone size >5mm. We then analyzed the association of hydronephrosis on EP-performed ultrasound, stone size >5mm, and proximal stone location with 30-day events. Methods: This was a prospective observational study of ED patients with suspected renal colic undergoing CT. Subjects had an EP-performed ultrasound evaluating for the severity of hydronephrosis. A chart review and follow-up phone call was performed. Results: We enrolled 302 subjects who had an EP-performed ultrasound. CT and EP ultrasound results were comparable in detecting severity of hydronephrosis ( x 2=51.7, p5mm less likely (NPV 89%; LR− 0.39). Larger stone size > 5mm was associated with 30-day events (OR 2.30, p=0.03). Conclusion: Using an ultrasound-first approach to detect hydronephrosis may help physicians identify patients with renal colic. The lack of hydronephrosis on ultrasound makes the presence of a larger ureteral stone less likely. Stone size >5mm may be a useful predictor of 30-day events

Ultrasound vs. Computed Tomography for Severity of Hydronephrosis and Its Importance in Renal Colic

Introduction: Supporting an “ultrasound-first” approach to evaluating renal colic in the emergency department (ED) remains important for improving patient care and decreasing healthcare costs. Our primary objective was to compare emergency physician (EP) ultrasound to computed tomography (CT) detection of hydronephrosis severity in patients with suspected renal colic. We calculated test characteristics of hydronephrosis on EP-performed ultrasound for detecting ureteral stones or ureteral stone size >5mm. We then analyzed the association of hydronephrosis on EP-performed ultrasound, stone size >5mm, and proximal stone location with 30-day events. Methods: This was a prospective observational study of ED patients with suspected renal colic undergoing CT. Subjects had an EP-performed ultrasound evaluating for the severity of hydronephrosis. A chart review and follow-up phone call was performed. Results: We enrolled 302 subjects who had an EP-performed ultrasound. CT and EP ultrasound results were comparable in detecting severity of hydronephrosis ( x 2=51.7, p5mm less likely (NPV 89%; LR− 0.39). Larger stone size > 5mm was associated with 30-day events (OR 2.30, p=0.03). Conclusion: Using an ultrasound-first approach to detect hydronephrosis may help physicians identify patients with renal colic. The lack of hydronephrosis on ultrasound makes the presence of a larger ureteral stone less likely. Stone size >5mm may be a useful predictor of 30-day events